Neoadjuvant Intralesional Daromun (L19IL2/L19TNF) in Resectable Locally Advanced Melanoma: An Update on the Efficacy and Safety Results of the PIVOTAL Phase III Trial
Abstract
Daromun (L19IL2/L19TNF) was investigated as a neoadjuvant, intralesional therapy for patients with fully resectable stage III melanoma in the phase III PIVOTAL trial (ClinicalTrials.gov identifier: NCT02938299 ). The trial enrolled 256 patients in the European Union and met its primary end point, demonstrating a statistically significant improvement in recurrence-free survival (RFS; hazard ratio, 0.59; P = .005) for daromun followed by surgery versus up-front surgery, at a median follow-up (FU) of 21 months from random assignment. PIVOTAL included two clinically distinct subgroups, namely, patients with de novo diagnosed metastatic disease (n = 34; 13%) and patients with recurrence(s) after surgery with or without radiotherapy and/or adjuvant systemic therapies (n = 222; 87%). Here, we present an updated analysis of the primary and secondary end points, including safety data, at a median FU of 36.8 months from random assignment (database cutoff: November 28, 2025), alongside new sensitivity analyses of event-free survival (EFS). The updated analysis confirms the clinically and statistically meaningful improvements in RFS and distant metastasis-free survival recorded in the neoadjuvant daromun versus control arm. The EFS post hoc analysis, conducted in both the overall population and the recurrent patient subgroups (with or without prior systemic therapies), provides consistency and robustness to the benefit of neoadjuvant daromun observed for the primary efficacy end point. No new safety signals of concern were recorded.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (26)
Axel Hauschild
Department of Dermatology, University Hospital, Kiel, Germany
Jessica Cecile Hassel
Department of Dermatology and NCT, Heidelberg University, Medical Faculty, University Hospital Heidelberg, Heidelberg, Germany
Mirjana Ziemer
Skin Cancer Center, University Hospital Leipzig, Leipzig, Germany
Piotr Rutkowski
Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
Friedegund Meier
Lukas Flatz
University Hospital Tübingen, Tübingen, Germany
Caroline Gaudy-Marqueste
From the Sandra and Edward Meyer Cancer Center (J.D.W.) and the Department of Medicine (J.D.W., M.A.P.), Weill Cornell Medicine, and Memorial Sloan Kettering Cancer Center (M.A.P.) — both in New York; Istituto Oncologico Veneto, IRCCS, Padua (V.C.-S.), European Institute of Oncology, IRCCS, Milan (P.Q.), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola (M.G.), University of Siena and the Center for Immuno-Oncology, University Hospital of Siena, Siena (M.M.), and Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.) — all in Italy; Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland (P.R.); Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.); University Hospital Essen, the German Cancer Consortium, the National Center for Tumor Diseases–West, the Research Alliance Ruhr, Research Center One Health, and University Duisburg-Essen — all in Essen, Germany (D.S.); the College of Medicine, Swansea University, Swansea (J.W.), Brist...
Mario Santinami
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Francesco Russano
IOV—Istituto Oncologico Veneto—IRCCS, Padua, Italy
Imke von Wasielewski
Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Hannover, Germany
Thomas Eigentler
Department of Dermatology, Venerology and Allergology, Charité-Universitaetsmedizin Berlin, Berlin, Germany
Michele Maio
From the Sandra and Edward Meyer Cancer Center (J.D.W.) and the Department of Medicine (J.D.W., M.A.P.), Weill Cornell Medicine, and Memorial Sloan Kettering Cancer Center (M.A.P.) — both in New York; Istituto Oncologico Veneto, IRCCS, Padua (V.C.-S.), European Institute of Oncology, IRCCS, Milan (P.Q.), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola (M.G.), University of Siena and the Center for Immuno-Oncology, University Hospital of Siena, Siena (M.M.), and Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.) — all in Italy; Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland (P.R.); Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.); University Hospital Essen, the German Cancer Consortium, the National Center for Tumor Diseases–West, the Research Alliance Ruhr, Research Center One Health, and University Duisburg-Essen — all in Essen, Germany (D.S.); the College of Medicine, Swansea University, Swansea (J.W.), Brist...
Iris Zalaudek
Sebastian Haferkamp
Pietro Quaglino
14University of Turin, Department of Medical Sciences, Dermatologic Clinic, Turin, Italy
Julia Welzel
Michael Weichenthal
Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel, Germany
Giuliano Elia
Philochem AG, Otelfingen, Switzerland
Alfredo Covelli
Philogen S.p.A., Siena, Italy
Katia Lorizzo
Philogen S.p.A., Siena, Italy
Agnese Parca
Philogen S.p.A., Siena, Italy
Dario Neri
Philochem AG
Paolo Antonio Ascierto
Università degli Studi di Napoli “Federico II” and Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, Italy
Caroline Robert
Dirk Schadendorf
Katharina Charlotte Kaehler
Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel, Germany